Navigating to a previously seen target without vision was unaffected by a 30-sec delay period at the beginning of the walking task. This study investigated whether a 60-sec delay, with or without a cognitive task, would modify the accuracy of reaching an 8-meter target. Thirty young adults participated. The delay, located at 0, 4, or 7 meters, was either to wait, or to count backwards. Kinematic data of distance travelled, distance-to-target, angular deviation, and body rotation from participants’ final position were recorded with a 3-D motion analysis system. Navigation precision was not significantly different with or without a delay, and whether or not the delays contained a cognitive task. However, comparisons among delays revealed a significant effect of delay position with larger distance errors occurring at the 0-meter delay in the 16 participants who walked at least 7 meters, suggesting that a delay at the beginning was more disruptive for navigation accuracy than when it occurred closer to the target.

No description available.

Animals perform a myriad of behaviors such as object tracking and spatial navigation, primarily in the absence of explicit target signals. In the absence of targets, neural circuits must implement a different target function. One primary theory for self-supervised learning is predictive learning, in which a system predicts feedforward signals over time, and in which internal representations emerge to provide longer-term structural information. While such theories are inspired by neural properties, they often lack direct links to low-level neural mechanisms. In the first study, a model of the formation of internal representations is presented. I introduce the canonical microcircuit of cortical structures, including general connectivity and unique physiological properties of neural subpopulations. I then introduce a learning rule based on the contrast of feedforward potentials in pyramidal neurons with their feedback-controlled burst rates. Utilizing these two signals the learning rule instantiates a feedback-gated temporal error minimization. Combined with a set of feedforward-only units and organized hierarchically, the model learns to tracks the dynamics of external stimuli with high accuracy, and successive regions are shown to code temporal derivatives of their feedforward inputs. The second study presents an electrophysiological experiment which showed a novel functional cell type in the retrosplenial cortex of behaving Long-Evans rats. Through rigorous statistical analysis we show that these neurons contain a egocentric representation of boundary locations. Combined with their location in the cortical hierarchy, this suggests that the retrosplenial neurons provide a mechanism for translating self-centered sensory information to the map-like representations present in subcortical structures. In the final study I integrate the basic modular architecture of the first study with the specific afferent stimuli and macroscale connectivity patterns involved in spatial navigation. I simulate an agent in a simple virtual environment and compare the learned representations to tuning curves from experiments such as study two. I find the expected development of neural responses corresponding to egocentric sensory representations (retrosplenial cortex), self-oriented allocentric coding (postrhinal cortex) and allocentric spatial representations (hippocampus). Together, these modeling results show how self-gated and guided learning in pyramidal ensembles can form useful and stable internal representations depending on the task at hand.

Yes / Early diagnosis of Alzheimer’s disease (AD) is essential if treatments are to be administered at an earlier point in time before neurons degenerate to a stage beyond repair. In order for early detection to occur tools used to detect the disorder must be sensitive to the earliest of cognitive impairments. Virtual reality (VR) technology offers opportunities to provide products which attempt to mimic daily life situations, as much as is possible, within the computational environment. This may be useful for the detection of cognitive difficulties. We develop a virtual simulation designed to assess visuospatial memory in order to investigate cognitive function in a group of healthy elderly participants and those with a mild cognitive impairment. Participants were required to guide themselves along a virtual path to reach a virtual destination which they were required to remember. The preliminary results indicate that this virtual simulation has the potential to be used for detection of early AD since significant correlations of scores on the virtual environment with existing neuropsychological tests were found. Furthermore, the test discriminated between healthy elderly participants and those with a mild cognitive impairment (MCI).

One of the earliest symptoms of Alzheimer’s Disease (AD) is a loss of spatial navigation. In this work, we improved an existing screening test for AD that analyzed a patient’s spatial navigation ability. The existing screening test was made more immersive, and therefore more reliable, by integrating support for a leading-edge consumer-targeted Head-Mounted Display (HMD). This integration brought some technical and usability challenges, that were addressed. Furthermore, we investigated the rehabilitative potential of Virtual Reality Navigational (VRN) activities in two case studies: an Early Stage AD (ESA) participant and a Late Stage AD (LSA) participant. We found that the ESA participant was able to significantly improve his navigation skills, and we observed some qualitative improvements in memory and navigation in his personal life. The LSA participant did not improve noticeably at the VRN tasks, but his mood improved after participating in the treatment sessions. These case studies suggested that VRN treatment may be beneficial for people with AD, especially at the onset stage. / February 2017

La navigation spatiale peut être subdivisée en deux processus: la construction d’une représentation mentale de l’espace à partir de l’exploration de l’environnement d'une part, et l’utilisation de cette représentation de façon à produire le trajet le plus adapté pour rejoindre le lieu souhaité d'autre part. Lors de l’exploration de l’environnement, des informations externes et des informations de mouvement propre (i.e. vestibulaires et proprioceptives) sont combinées pour former la carte cognitive. Depuis longtemps des études suggèrent que le cervelet participe à la navigation spatiale mais son rôle a souvent été confiné à l’exécution motrice. Notre équipe a étudié des souris mutantes L7-PKCI présentant un déficit de plasticité synaptique de type dépression à long terme (DLT) au niveau des synapses entre fibres parallèles et cellules de Purkinje du cortex cérébelleux. Ces travaux ont montré que les souris présentent à la fois un déficit dans l'optimisation de la trajectoire mais également dans le maintien de la carte cognitive formée dans l'hippocampe. En effet, les propriétés de décharge des cellules de lieu de l'hippocampe sont affectées chez ces souris exclusivement lorsque celles-ci doivent naviguer en se reposant sur les informations provenant de leur mouvement propre, c'est à dire quand elles explorent l'environnement dans le noir. A ces mêmes synapses, une plasticité de type potentialisation à long terme (PLT) a été observée et permet (avec la DLT) la modulation bidirectionelle de l’efficacité synaptique. La plasticité bidirectionnelle est un processus clé dans les modèles théoriques de type « filtre adaptatif » de traitement de l’information par le cervelet. Selon ces modèles, l’absence de PLT ou DLT devrait affecter de façon similaire la plasticité bidirectionnelle et conduire ainsi à des déficits comparables. Pour tester cette hypothèse, nous avons étudié les conséquences fonctionnelles d’un déficit de type PLT au niveau de la même synapse entre fibre parallèle et cellule de Purkinje. Nous avons utilisé la lignée transgénique L7-PP2B, spécifiquement déficitaire pour cette plasticité.Malgré un léger déficit moteur révélé exclusivement sur le rotarod, les capacités de navigation des souris L7-PP2B ne sont pas affectées dans une tâche de navigation en labyrinthe aquatique de type piscine de Morris. Les propriétés des cellules de lieu de l’hippocampe des souris L7-PP2B ont ensuite été caractérisées lors de l’exploration d’une arène circulaire dans différentes conditions environnementales. Contrairement à celles des souris L7-PKCI, les propriétés des cellules de lieux des souris L7-PP2B ne sont pas affectées lorsque les souris ne peuvent utiliser que les informations de mouvement propre pour s’orienter, c'est à dire dans le noir. Par contre, les cellules de lieux des souris L7-PP2B présentent une instabilité en l’absence de toute manipulation d’indice environnemental, dans 23% des sessions d’enregistrement. Cette instabilité, absente chez les souris contrôles, se manifeste de façon imprévisible dans un environnement familier et est caractérisée par une rotation angulaire cohérente de l’ensemble des cellules de lieux enregistrées. Ces données suggèrent qu’en l’absence de PLT cérébelleuse la représentation spatiale de l’hippocampe n’est pas ancrée de façon stable aux indices externes proximaux. Ces résultats, associés à ceux des souris L7-PKCI indiquent que le cervelet contribue de manière complexe à la fois à la représentation spatiale hippocampique et aux capacités de navigation et que DLT et PLT jouent probablement des rôles différents dans ces processus. / Spatial navigation can be divided into two processes: building a spatial representation from the environment exploration and using this representation to produce an adapted trajectory toward a goal. During the environment exploration, external and self-motion information (i.e. vestibular and proprioceptive) are combined to form the spatial map. It has long been suggested that the cerebellum participates in spatial navigation but its role has often been confined to motor execution. Our team has studied L7-PKCI mice which lack a plasticity mechanism (long term depression (LTD)) at parallel fiber-Purkinje cell synapses in the cerebellar cortex. These works have shown that L7-PKCI mice present a deficit in trajectory optimization as well as in the maintenance of the cognitive map in the hippocampus. Indeed in these mice, the firing properties of hippocampal place cells are affected specifically when mice have to rely on self-motion information, i.e. when exploring the environment in the dark.A these same synapses, another type of plasticity (long term potentiation (LTP)) has been described, and allows (with LTD) the bidirectional modulation of the synaptic efficiency. Bidirectional plasticity is a key element of the ‘adaptive filter’ theoretical models of cerebellar information processing. According to these models, a lack of LTP or LTD should similarly affect bidirectional plasticity and result in comparable deficits. To test this prediction, we investigated the functional consequences of a deficit of LTP at parallel fiber-Purkinje cell synapses using the L7-PP2B mice model, specifically impaired for this plasticity.In spite of a mild motor adaptation deficit, revealed on the rotarod task, spatial learning of L7-PP2B mice was not impaired in the watermaze task. Hippocampal place cell properties of L7-PP2B mice were characterized during exploration of a circular arena, following different experimental manipulations. In contrast to mice lacking cerebellar LTD, place cells properties of L7-PP2B mice were not impaired when mice had to rely on self-motion cues, i.e. in the dark. Surprisingly, L7-PP2B place cells displayed instability in the absence of any proximal cue manipulation in 23 % of the recording sessions. This instability occurred in an unpredictable way in a familiar environment and was characterized each time by a coherent angular rotation of the whole set of recorded place cells. These data suggest that, in the absence of cerebellar LTP, hippocampal spatial representation cannot be reliably anchored to the proximal cue. These results along with those from L7­PKCI mice, indicate that the cerebellum contributes to both hippocampal representation and subsequent navigation abilities and that LTP and LTD are likely to play different roles in these processes.

<p>Estradiol modulates the use of spatial navigation strategies in female rats. The presence of circulating estradiol enhances learning on tasks that require the use of a hippocampus-dependent place strategy and impairs learning on tasks that require the use of a dorsal striatum-dependent response strategy. When either strategy may be used successfully, estradiol biases females to use a place strategy. While this behavioral effect has been well-described in the young adult female rat, little is known about the mechanisms in the brain that underlie it or how it changes across age. The experiments in this dissertation examined how age, previous experience, and hormonal condition affect the ability of estradiol to modulate learning during explicit training of place and response tasks, as well as navigation strategy use during ambiguous navigation tasks. Age highly influenced the ability of estradiol to influence strategy use. While female rats could use place and response strategies to navigate by postnatal day (PD) 21, estradiol did not bias them to use a response strategy until PD26, just before puberty. In adulthood, previous navigation experience and estradiol interacted to influence navigation strategy use on a series of experiences to an ambiguous navigation task. And, estradiol impaired learning during explicit response training but did not affect place learning. In middle age, estradiol further impaired response learning but still did not affect place learning. Long-term hormone deprivation, however, was detrimental to acquisition of a place task but did not affect response learning. These experiments also examined the effects of estradiol on activity, plasticity, and reliability of neuronal ensembles in several subregions of the hippocampus and striatum during spatial navigation using cellular and molecular techniques that take advantage of the kinetics of the immediate-early genes c-fos and Arc. Increased activation and plasticity during active exploration across several subregions of the hippocampus and striatum reflected similar inputs to these neural systems and similar effects of exploration. However, estradiol modulated the plasticity and reliability of neuronal ensembles in the hippocampus and striatum specifically during goal-directed spatial navigation. Estradiol increased plasticity in CA1 of all behaviorally-trained rats, but only place strategy users displayed high reliability in this plasticity across training and probe trials on a navigation task. Estradiol prevented increase in plasticity and reliability in the dorsolateral striatum displayed by low estradiol response strategy users. These experiments reveal how several factors, including age, influence estradiol's modulation of spatial navigation strategy use and suggest functional mechanisms by which this modulation occurs.</p> / Dissertation

Considerable research has examined strategies involved in spatial navigation, and what factors determine which strategy an individual will use. The little research that has examined strategy adoption has produced conflicting results. The present study investigated the relative rate of adoption of allocentric and egocentric strategies in an environment that allowed individuals to adopt one or the other, or switch between them. Results indicated that by the end of testing nearly all participants had adopted one strategy or the other. Also, more participants were using an allocentric strategy than an egocentric strategy. However, strategy selection was not related to gender, or the relative efficiency of the two strategies. Analysis of gaze position at the start of trials showed that those who adopted an allocentric strategy tended to focus their attention on the distal (landscape) features of the environment whereas those who adopted an egocentric strategy tended to focus their attention on the proximal object features. However, vertical gaze position could not be used to reveal the rate of adoption of an egocentric strategy, because this did not vary over trials. Analysis of gaze position using “regions of interest” overcame this problem and showed that both strategies are adopted at a similar rate early in trials. Comparison of strategy by gaze position and strategy by navigation probe indicated that these two metrics were measuring two different stages of navigation. Finally, analysis of the navigational efficiency of different strategies indicated that the best navigators were those who used both strategies. These findings indicate allocentric and egocentric strategies are adopted at a similar rate and that within the space of a few seconds, individuals may use different strategies for orientation and navigation. / Graduate

This dissertation is a compendium of multiple research papers that, together, address two main objectives. The first objective and primary research question is to determine whether or not, through a procedure of independent component analysis (ICA)-based data mining, volume-domain validation, and source volume estimation, it is possible to construct a meaningful, objective, and informative model of brain activity from scalpacquired EEG data. Given that a methodology to construct such a model can be created, the secondary objective and research question investigated is whether or not the sources derived from the EEG data can be used to construct a model of complex brain function associated with the spatial navigation and the virtual Morris Water Task (vMWT). The assumptions of the signal and noise characteristics of scalp-acquired EEG data were discussed in the context of what is currently known about functional brain activity to identify appropriate characteristics by which to separate the activities comprising EEG data into parts. A new EEG analysis methodology was developed using both synthetic and real EEG data that encompasses novel algorithms for (1) data-mining of the EEG to obtain the activities of individual areas of the brain, (2) anatomical modeling of brain sources that provides information about the 3-dimensional volumes from which each of the activities separated from the EEG originates, and (3) validation of data mining results to determine if a source activity found via the data-mining step originates from a distinct modular unit inside the head or if it is an artefact. The methodology incorporating the algorithms developed was demonstrated for EEG data collected from study participants while they navigated a computer-based virtual maze environment. The brain activities of participants were meaningfully depicted via brain source volume estimation and representation of the activity relationships of multiple areas of the brain. A case study was used to demonstrate the analysis methodology as applied to the EEG of an individual person. In a second study, a group EEG dataset was investigated and activity relationships between areas of the brain for participants of the group study were individually depicted to show how brain activities of individuals can be compared to the group. The results presented in this dissertation support the conclusion that it is feasible to use ICA-based data mining to construct a physiological model of coordinated parts of the brain related to the vMWT from scalp-recorded EEG data. The methodology was successful in creating an objective and informative model of brain activity from EEG data. Furthermore, the evidence presented indicates that this methodology can be used to provide meaningful evaluation of the brain activities of individual persons and to make comparisons of individual persons against a group. In sum, the main contributions of this body of work are 5 fold. The technical contributions are: (1) a new data mining algorithm tailored for EEG, (2) an EEG component validation algorithm that identifies noise components via their poor representation in a head model, (3) a volume estimation algorithm that estimates the region in the brain from which each source waveform found via data mining originates, (4) a new procedure to study brain activities associated with spatial navigation. The main contribution of this work to the understanding of brain function is (5) evidence of specific functional systems within the brain that are used while persons participate in the vMWT paradigm (Livingstone and Skelton, 2007) examining spatial navigation. / Graduate / 0541 / 0622 / 0623

The goal of this study was to examine differences in the exploratory activity, spatial learning and memory between two strictly subterranean rodents with different social systems, solitary silvery mole-rat (Heliophobius argenteocinereus) and social giant mole-rat (Fukomys mechowii) in a maze resembling natural burrows. Although the giant mole-rats showed better performance in most of the parameters of the test, this could not be easily explained by superior learning abilities of social species. The differences found could be more attributed to different motivation in both species. The solitary mole-rat was remarkably more cautious and moved with lower velocity, spent more time in the maze, made more errors and traveled a longer path before reaching the reward box.